Severe imported Plasmodium falciparum malaria, France, 1996-2003.

Little is known about severe imported Plasmodium falciparum malaria in industrialized countries where the disease is not endemic because most studies have been case reports or have included <200 patients. To identify factors independently associated with the severity of P. falciparum, we conducted a retrospective study using surveillance data obtained from 21,888 P. falciparum patients in France during 1996-2003; 832 were classified as having severe malaria. The global case-fatality rate was 0.4% and the rate of severe malaria was ≈3.8%. Factors independently associated with severe imported P. falciparum malaria were older age, European origin, travel to eastern Africa, absence of chemoprophylaxis, initial visit to a general practitioner, time to diagnosis of 4 to 12 days, and diagnosis during the fall-winter season. Pretravel advice should take into account these factors and promote the use of antimalarial chemoprophylaxis for every traveler, with a particular focus on nonimmune travelers and elderly persons.

Fatal cerebral malaria diagnosed after death in a French patient.

We report on the case of a French citizen who was found dead in his home, 4 days after returning from Cameroon. The patient died of imported malaria, as revealed by the postmortem investigations. Few such cases have been reported throughout the world. This article reviews deaths due to malaria diagnosed at the time of autopsy in France between 1995 and 2005. We conclude that the nonspecific symptoms of malaria can lead to a misdiagnosis and the need for a forensic expert to intervene at the scene of death, which usually occurs in the home. We will remind forensic pathologists of the clinical, biologic, and forensic aspects of this infectious disease. In particular, the uses of microbiologic analyses, the QBC malaria test and the Core malaria Pan/Pv/pf test as well as brain tissue histology will be reviewed.

Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base.

BACKGROUND: Halofantrine (HF) was considered an effective and safe treatment for multi-drug resistant falciparum malaria until 1993, when the first case of drug-associated death was reported. Since then, numerous studies have confirmed cardiac arrythmias, possibly fatal, in both adults and children. The aim of the study was to review fatal HF related cardiotoxicity. METHODS: In addition, to a systematic review of the literature, the authors have had access to the global safety database on possible HF related cardiotoxicity provided by GlaxoSmithKline. RESULTS: Thirty-five cases of fatal cardiotoxicity related to HF, including five children, were identified. Females (70%) and patients from developing countries (71%) were over-represented in this series. Seventy-four percent of the fatal events occurred within 24 hours of initial exposure to HF. Twenty six patients (74%) had at least one predisposing factor for severe cardiotoxicity, e.g., underlying cardiac disease, higher than recommended doses, or presence of a concomitant QT-lengthening drug. All (100%) of the paediatric cases had either a contraindication to HF or an improper dose was given. In six cases there was no malaria. CONCLUSION: A distinction should be made between common but asymptomatic QT-interval prolongation and the much less common ventricular arrhythmias, such as torsades de pointes, which can be fatal and seem to occur in a very limited number of patients. The majority of reported cardiac events occurred either in patients with predisposing factors or with an improper dose.Therefore, in the rare situations in which HF is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females.

Atypical aetiology of a conjugal fever: autochthonous airport malaria between Paris and French Riviera: a case report.

Endemic malaria has been eradicated from France, but some falciparum malaria cases have been described in patients who have never travelled outside the country. Ms. V. 21 year-old and Mr. M. 23 year-old living together in Paris were on holiday in Saint Raphaël (French Riviera). They presented with fever, vertigo and nausea. A blood smear made to control thrombocytopaenia revealed intra-erythrocytic forms of Plasmodium falciparum. The parasitaemia level was 0.15% for Ms. V and 3.2% for Mr. M. This couple had no history of blood transfusion or intravenous drug use. They had never travelled outside metropolitan France, but had recently travelled around France: to Saint Mard (close to Paris Charles de Gaulle (CdG) airport), to Barneville plage (in Normandy) and finally to Saint Raphaël. The most probable hypothesis is an infection transmitted in Saint Mard by an imported anopheline mosquito at CdG airport. The DNA analysis of parasites from Ms. V.'s and Mr. M.'s blood revealed identical genotypes. Because it is unlikely that two different anopheline mosquitoes would be infected by exactly the same clones, the two infections must have been caused by the infective bites of the same infected mosquito.

The risk of malaria in travelers to India.

BACKGROUND: Several countries have reported a decline in malaria cases imported by travelers returning from India. METHODS: We collected data on imported malaria for the period 1992 to 2005 from nine countries. Traveler statistics denominator data were obtained from the Indian Ministry of Tourism. RESULTS: The malaria case numbers declined from 93 cases per 100,000 travelers in 1992 to 19 cases per 100,000 travelers in 2005. The proportion of Plasmodium falciparum decreased steadily throughout the years. The proportion of Plasmodium vivax accounts for more than 80% of all cases of malaria in travelers to India. Deaths due to malaria were rare; only the UK and the United States reported deaths, a total of 16, between 1992 and 2005. The high-risk areas for malaria in India can be clearly identified using endemic malaria data. High-risk states are Chhattisgarh, Orissa, Jharkhand, West Bengal, Goa (mainly P vivax), and the states east of Bangladesh. CONCLUSIONS: The decreasing incidence of malaria in travelers to India and the high proportion of P vivax support the current change in guidelines in some European countries advocating the use of the standby emergency self-treatment strategy or bite precautions plus awareness of risk instead of chemoprophylaxis. Otherwise in high-risk states, chemoprophylaxis should still be considered particularly in high-transmission seasons.

Imported malaria in children in industrialized countries, 1992-2002.

Children account for an appreciable proportion of total imported malaria cases, yet few studies have quantified these cases, identified trends, or suggested evidence-based prevention strategies for this group of travelers. We therefore sought to identify numbers of cases and deaths, Plasmodium species, place of malaria acquisition, preventive measures used, and national origin of malaria in children. We analyzed retrospective data from Australia, Denmark, France, Germany, Italy, Japan, the Netherlands, Sweden, Switzerland, the United Kingdom, and the United States and data provided by the United Nations World Tourism Organization. During 1992-2002, >17,000 cases of imported malaria in children were reported in 11 countries where malaria is not endemic; most (>70%) had been acquired in Africa. Returning to country of origin to visit friends and relatives was a risk factor. Malaria prevention for children should be a responsibility of healthcare providers and should be subsidized for low-income travelers to high-risk areas.

Health problems in returning travelers consulting general practitioners.

Over a 2-month period, 43 of 143 participating general practitioners included 97 patients with 113 health impairments, mainly gastrointestinal problems (35%), respiratory tract infections (30%), and skin diseases (11%). Systemic febrile illness or imported tropical disease accounted for less than 4% of cases.

The low and declining risk of malaria in travellers to Latin America: is there still an indication for chemoprophylaxis?

A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers. Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest API's in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.

Risk factors for imported fatal Plasmodium falciparum malaria, France, 1996-2003.

Plasmodium falciparum malaria is a serious health hazard for travelers to malaria-endemic areas and is often diagnosed on return to the country of residence. We conducted a retrospective study of imported falciparum malaria among travelers returning to France from malaria-endemic areas from 1996 through 2003. Epidemiologic, clinical, and parasitologic data were collected by a network of 120 laboratories. Factors associated with fatal malaria were identified by logistic regression analysis. During the study period, 21,888 falciparum malaria cases were reported. There were 96 deaths, for a case-fatality rate of 4.4 per 1,000 cases of falciparum malaria. In multivariate analysis, risk factors independently associated with death from imported malaria were older age, European origin, travel to East Africa, and absence of chemoprophylaxis. Fatal imported malaria remains rare and preventable. Pretravel advice and malaria management should take into account these risk factors, particularly for senior travelers.

[Epidemiology of malaria]. / Epidémiologie du paludisme.

Four parasite species, among which one lethal, at least 20 efficient vectors, spread on the most crowded and underdeveloped continents, where first antimalarials and insecticides were so extensively used for decades that they are now inefficient after resistances. It is today the sad medium on which malaria raged, spring of 1 million deaths and 300 millions cases a year, of which 90% in sub-Saharan Africa. In Africa, epidemiological patterns are widely different some to others, which explain unique control strategy failure and vanity. Waiting vaccines and new drugs, control must be centred on vectors control and multidrug therapy. France is the industrialised country with the highest number of imported cases (approximately equal to 7000 cases yearly), linked mainly to P. falciparum coming from sub-Saharan Africa and recurring in nearly 3/4 of cases in immigrants.

[Malaria: what about exposure prophylaxis?]. / Paludisme: où en est la prophylaxie d'exposition?

Malaria would not exist without mosquito bites. The growing resistance to antimalarial drugs has led to an increasing role of personal protection measures. However, insect repellents are not evaluated as medicinal products, and many products available on the market contain active substances that have been poorly evaluated or present in insufficient doses. The efficacy of the most active insect repellents, DEET and icaridin/KBR 3023, like that of medicinal products, is limited by the subject's compliance, bearing in mind that the Anopheles bite is painless and that humans are primarily bothered by the nuisance factor of the mosquito.

[Malaria chemoprophylaxis in 2005: new policy, new drugs]. / Chimioprophylaxie du paludisme: nouvelles stratégies, nouvelles molécules.

For a traveller visiting highly endemic areas for malaria (mainly sub-Saharan Africa), the use of a chemoprophylaxis has to be considered as mandatory in addition to exposure prophylaxis measures (including in migrants largely over-represented among returning travellers with imported malaria). The choice of the appropriate drug depends mainly on the visited area with regard to the level of resistance to chloroquine. Due to the spread of resistance, 7 countries along the West African coast between Senegal and Côte d'Ivoire moved in 2005 from zone 2 to zone 3 (according to the French classification). Recently available and recommanded in zones 2 and 3, the atovaquone+proguanil combination appears to be of great interest due to a good tolerance and an intake limited to the 7 days following return. Alternatively to mefloquine or atovaquone+proguanil, the well tolerated and cheap doxycycline is a good choice but due to its short half life a full compliance is mandatory. In case of fever, even if a chemoprophylaxis is taken, malaria can develop, sometimes with atypical presentations, and has to be systematically considered.